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Research Paper
Depletion of Procathepsin D Gene Expression by RNA Interference – A Potential Therapeutic Target for Breast Cancer
Sujata S. Ohri, Aruna Vashishta, Mary Proctor, Martin Fusek and Vaclav Vetvicka
volume 6 | issue 7
July 2007Pages: 1081 - 1087
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Elevated level of procathepsin D (pCD), a zymogen of lysosomal aspartic proteinase cathepsin D, is associated with highly invasive neoplasms that include breast cancer. Independent studies have established that secreted pCD functions as a growth factor acting both in an autocrine and paracrine manner. Therefore, to explore whether pCD can be employed as a therapeutic target, the present study evaluates the impact of pCD knockdown using RNA interference technology. Of the three siRNA oligos tested, siRNA-3 exhibited a 90% inhibitory effect on pCD gene expression. Stable attenuation of pCD in breast cancer cells MDA-MB-231 was achieved by using a plasmid vector-based shRNA system. Pronounced suppression of pCD expression was accompanied by a significant reduction in invasion and proliferation of MDA-MB-231 cells stably transfected with functional shRNA. Importantly, in the athymic nude mice model, downregulation of pCD in breast cancer cells significantly reduced their metastatic potential. In addition, we observed a reduction in Cdc42 and NF-κB2 expression in MDA-MB-231 cells with decreased pCD expression. When combined, our in vitro and in vivo experiments demonstrate that targeting pCD through RNAi technology represents a potential therapeutic tool for developing a therapy against breast cancer.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.